Investigating fundamental properties and clinical applications of the optoretinogram

摘要 这笔赠款将研究视视网膜图（ORG）——一种对人类感光器进行实验性全光学测定的方法 功能——及其揭示细胞水平功能障碍的潜力。 ORG 基于自适应光学 相干断层扫描 (AOOCT)，这是生成活人视网膜 3D 图像的唯一现有方法 具有细胞分辨率。它利用了我们的新观察结果，即光刺激会导致大脑中的微观变形。 活的光感受器外段 (OS)，以及 OCT 对组织变形的敏感性要小得多 比成像源的波长。目标 1 研究 ORG 测量视杆细胞和视杆细胞功能的能力 锥体，通过测量正常受试者的反应并表征信号对刺激变化的敏感性 lus 能量，以及影响这种敏感性的因素，例如响应的空间和时间方差、计算 因素和光子噪声。目标 2 研究光诱发操作系统变形的机制。我们会 严格确定变形饱和时的光照水平、多次闪光的效果，以及 信号对视网膜偏心率的依赖性，所有这些都提供了有关生化的有价值的信息 导致观察到的变形的过程。目标 3 将 ORG 应用于特征明确的视网膜疾病， 确定它是否能够检测患有已知缺陷的光感受器的病理功能障碍。 充分表征的缺陷反过来又提供了可能为生化和生物群落带来启示的自然实验 操作系统中观察到的光诱发变形的机械决定因素。

Abstract This grant will investigate the optoretinogram (ORG)–an experimental, all optical assay of human photoreceptor function–and its potential to reveal dysfunction at the cellular level. The ORG is based on adaptive optics optical coherence tomography (AO­OCT), which is the only existing way to produce 3D images of the living human retina with cellular resolution. It leverage our novel observation that light stimuli cause microscopic deformations in the living photoreceptor outer segment (OS), along with OCT’s sensitivity to deformations in the tissue much smaller than the wavelength of the imaging source. Aim 1 investigates the ORG’s ability to measure function in rods and cones, by measuring responses in normal subjects and characterizing the signal’s sensitivity to changes in stimu­ lus energy, and factors affecting this sensitivity, such as spatial and temporal variance in response, computational factors, and photon noise. Aim 2 investigates the mechanisms underlying light­evoked OS deformation. We will rigorously determine the light levels at which the deformations are saturated, the effect of multiple flashes, and the signal’s dependence on retinal eccentricity, all of which provide valuable information about the biochemical processes causing the observed deformations. Aim 3 applies the ORG to well­characterized retinal disease, to determine whether it is able to detect pathological dysfunction in photoreceptors suffering from known deficits. Well­characterized deficits, in turn, offer natural experiments which may shed light on the biochemical and biome­ chanical determinants of the observed light­evoked deformations in the OS.